Liver Damage After Paracetamol Overdose Comparison of Liver-Function Tests, Fasting Serum Bile Acids, and Liver Histology

James, Oliver; Roberts, Susan H.; Douglas, A.G.; Lesna, M.; Pulman, L.; Smith, Pamela Alethea; Watson, Alexander

doi:10.1016/s0140-6736(75)90170-1

Cited by 89 publications

(29 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When these bile acids returned to normal levels at 168 h it may indicate that the liver was functioning and recovered from injury. Total serum bile acids levels in acetaminophen overdose patients have reported to be more sensitive of mild liver damage than transaminases [38]. These findings are consistent with a previous report that found serum bile acid levels could be more sensitive biomarkers of organic solvent-induced hepatotoxicity than traditional ALT, AST, GGT and ALP [39].…”

Section: Discussionsupporting

confidence: 90%

Systems Biology Investigation to Discover Metabolic Biomarkers of Acetaminophen-Induced Hepatic Injury Using Integrated Transcriptomics and Metabolomics

2013

J Mol Biomark Diagn

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 90%

Systems Biology Investigation to Discover Metabolic Biomarkers of Acetaminophen-Induced Hepatic Injury Using Integrated Transcriptomics and Metabolomics

2013

J Mol Biomark Diagn

View full text Add to dashboard Cite

“…Aminotransferases may increase excessively and abruptly during toxic hepatitis. However, alone these tests are insufficient to indicate the severity of liver damage and the prognosis; they are less effective than histopathological examination (20,21). In this study, AST and ALT levels in the Cis group were higher than in the CIN group.…”

Section: Discussioncontrasting

confidence: 56%

Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

et al. 2016

View full text Add to dashboard Cite

“…These observations should be interpreted with caution. Our model of bile acid homeostasis is based on physiological values for bile acid concentrations in the blood and the liver and tracks well with dose-response results from patients with APAP overdose (James et al, 1975). However, we were unable to find reports of a time course of blood bile acids after APAP overdose, and as such we do not know whether the time course of blood bile acids in our model is an accurate representation of what is seen in the clinic.…”

Section: Nac Treatment Analysis Using a Systems Model Of The Liver 537mentioning

confidence: 75%

An Analysis ofN-Acetylcysteine Treatment for Acetaminophen Overdose Using a Systems Model of Drug-Induced Liver Injury

Woodhead

Howell²,

Yang³

et al. 2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

N-acetylcysteine (NAC) is the treatment of choice for acetaminophen poisoning; standard 72-h oral or 21-h intravenous protocols are most frequently used. There is controversy regarding which protocol is optimal and whether the full treatment course is always necessary. It would be challenging to address these questions in a clinical trial. We used DILIsym, a mechanistic simulation of drug-induced liver injury, to investigate optimal NAC treatment after a single acetaminophen overdose for an average patient and a sample population (n ϭ 957). For patients presenting within 24 h of ingestion, we found that the oral NAC protocol preserves more hepatocytes than the 21-h intravenous protocol. In various modeled scenarios, we found that the 21-h NAC infusion is often too short, whereas the full 72-h oral course is often unnecessary. We found that there is generally a good correlation between the time taken to reach peak serum alanine aminotransferase (ALT) and the time taken to clear N-acetyl-p-benzoquinone imine (NAPQI) from the liver. We also found that the most frequently used treatment nomograms underestimate the risk for patients presenting within 8 h of overdose ingestion. V max for acetaminophen bioactivation to NAPQI was the most important variable in the model in determining interpatient differences in susceptibility. In conclusion, DILIsym predicts that the oral NAC treatment protocol, or an intravenous protocol with identical dosing, is superior to the 21-h intravenous protocol and ALT is the optimal available biomarker for discontinuation of the therapy. The modeling also suggests that modification of the current treatment nomograms should be considered.

show abstract

Liver Damage After Paracetamol Overdose Comparison of Liver-Function Tests, Fasting Serum Bile Acids, and Liver Histology

Cited by 89 publications

References 9 publications

Systems Biology Investigation to Discover Metabolic Biomarkers of Acetaminophen-Induced Hepatic Injury Using Integrated Transcriptomics and Metabolomics

Systems Biology Investigation to Discover Metabolic Biomarkers of Acetaminophen-Induced Hepatic Injury Using Integrated Transcriptomics and Metabolomics

Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

An Analysis ofN-Acetylcysteine Treatment for Acetaminophen Overdose Using a Systems Model of Drug-Induced Liver Injury

Contact Info

Product

Resources

About